The chronic inflammatory reaction of atherosclerosis remodels major vessels. LDL oxidation is an early event that may be causal, but certainly contributes to the disease process because it creates inflammatory mediators that attract monocytes, and activates vascular cells and these infiltrating monocytes. Monocytes store intracellular lipids following uptake of oxidized LDL, aided by the scavenger receptor CD36, to form foam cells. Oxidized LDL is atherogenic, and it is phospholipid oxidation that changes LDL behavior. Phospholipid oxidation products, we find, are biologically active because some engage and stimulate the receptor for the inflammatory phospholipid platelet-activating factor (PAF), while others potently bind and activate the nuclear hormone receptor and transcription factor PPARgamma. PPARgamma is present in atherosclerotic lesions where it controls expression of CD36 and foam cell formation. Conversely at higher concentrations oxidized LDL becomes toxic, with less being known about the molecules that cause apoptosis. The cytokine MCP-1 is essential for atherogenesis, and PAF-like lipids and PPAR gamma agonists induce its synthesis under different conditions. We now find that there is a third, currently undefined, route to the induction of the key, pro-atherogenic cytokine MCP-1. Oxidized phospholipids therefore act at several levels, from gene induction to apoptosis, in atherogenesis. We propose that: 1) the PPARy ligands that control the function of the transcription factor PPARgamma are present in atherosclerotic lesions. 2) undefined PPAR gamma-dependent and PPAR gamma-independent mechanisms induce MCP-1 synthesis following LDL oxidation. 3) oxidized phospholipids are early, common, and essential components of apoptosis 4) display of oxidized phosphatidylserine on the surface of apoptotic cells marks them for macrophage engulfment, which subsequently activates these phagocytes. 5) all these events are controlled by the oxidized phospholipid phospholipase PAF acetylhydrolase.